Stapokibart for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps
Shen Shen, Bing Yan, Ming Wang, Di Wu, Yingshi Piao, Jun Tang, Xiangli Yang, Zhiwei Cao, Jinmei Xue, Wenwen Liu, Shixi Liu, Li Shi, Guangke Wang, Xicheng Song, Yongtian Lu, Jianjun Chen, Luyun Jiang, Jing Ye, Shaoqing Yu, Yucheng Yang, Hongyan Fang, Jiping Li, Haibo Shi, Jiangang Fan, Hongyue Yan, Haifei Wang, Bo Chen, Chengshuo Wang, Luo Zhang, CROWNS-2 Study Investigators, Lijia Wan, Guolin Tan, Yi Yang, Shiyin Ma, Lizhong Su, Xuezhong Li, Yongle Li, Fang Quan, Mingliang Xiang, Yan Jiang, Gang He, Chang Lin, Xiaoyong Ren, Liyan Ni, Xiaoping Gao, Jiusheng Chu, Ruixia Ma, Zhihai Xie, Bing Guan, Shui‐Hong Zhou, Lijian Zhang, Xin Wei, Zhichun Huang, Qingshan Jiang, Xin Wang, Li Zhu, Zian Xiao, Lei Cheng, Kai Wang, Qingqing Yu, Jing Pan, Yuxiao Du, Xiaoqiu Chen, Rui Dong, Shi‐Ping Sun, Feng Liu, Shengyang Liu, Pengfei Ba, Yu Zhang, Xiaobin Wang, Shan Chen, Yan Xie, Qing Luo, Ling Jin, Xia Ke, Junwei Xiong, Ji Xu, Weitian Zhang, Qinxuan Gu, Wei Ni, Wei Li, Xia Gong, Junjie Zhang, Weiming Hu, Shuang Gu, Zhiqi Ma, Huajing Li, Yilin Shen, Longgang Yu, Ding-qiang Huang, Yuanteng Xu, Bin Sun, Xuejun Liu, Hui Shao, Yanyun Liu, Le Wang, Shumin Xie, Haihong Chen, Zhuoqin Han, Jing Zheng
Abstract
Importance: Chronic rhinosinusitis with nasal polyps causes severe symptoms and impaired quality of life. Stapokibart is a novel monoclonal antibody that targets interleukin 4Rα. Objective: To assess the efficacy and safety of stapokibart as an add-on treatment to intranasal corticosteroids in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps. Design, Setting, and Participants: From August 9, 2022, to April 28, 2023, this randomized, double-blind, phase 3 clinical trial, conducted at 51 hospitals in China, enrolled adult patients with chronic rhinosinusitis with nasal polyps who had a history of systemic corticosteroid use or sinonasal surgery and a bilateral nasal polyp score of 5 or greater (on a scale of 0-8) and a weekly mean nasal congestion score of 2 or greater (on a scale of 0-3). Eosinophilic chronic rhinosinusitis with nasal polyps was defined as blood eosinophils of 6.9% or greater (without asthma) or 3.7% or greater (with asthma) or an eosinophil count of 55 per high-power field or greater or 27% or greater in nasal polyp tissue. Patient follow-up was completed on June 25, 2024. Interventions: Four weeks after initiation of mometasone furoate nasal spray, 100 µg in each nostril daily, patients were randomized to receive subcutaneous stapokibart, 300 mg, or placebo (1:1) every 2 weeks for 24 weeks. Both groups then received stapokibart for 28 weeks. Main Outcomes and Measures: Co-primary end points were changes from baseline in nasal polyp score (meaningful change threshold [MCT] ≥1 point) and nasal congestion score (MCT ≥0.5 points) at week 24 in all patients and in the population with eosinophilia. Results: Among 180 patients randomized, 179 (mean age, 45 [SD, 12.9] years; 61 [34.1%] women) received at least 1 treatment dose (n = 90 for stapokibart; n = 89 for placebo). In the overall population, the least-squares (LS) mean change in nasal polyp score from baseline to week 24 in the stapokibart vs placebo groups was -2.6 vs -0.3 points, respectively, (LS mean difference, -2.3; 95% CI, -2.6 to -1.9; P < .001); in the population with eosinophilia, the change was -3.0 vs -0.4 points, respectively (LS mean difference, -2.5; 95% CI, -2.9 to -2.1; P < .001). The LS mean change in nasal congestion score from baseline to week 24 in the stapokibart vs placebo groups was -1.2 vs -0.5 points, respectively, in the overall population (LS mean difference, -0.7; 95% CI, -0.9 to -0.5; P < .001) and -1.3 vs -0.5 points, respectively, in the population with eosinophilia (LS mean difference, -0.8; 95% CI, -1.0 to -0.6; P < .001). Serious adverse events were rare (2.2% in the stapokibart group vs 1.1% in the placebo group). Higher rates of arthralgia (7.8% vs 0%) and hyperuricemia (5.6% vs 1.1%) were reported with stapokibart vs placebo, respectively. Conclusions and Relevance: Among patients with severe chronic rhinosinusitis with nasal polyps treated with a daily intranasal corticosteroid, stapokibart reduced polyp size and severity of nasal symptoms at 24 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05436275.